EANM procedure guideline for brain perfusion SPECT using 99mTc-labelled radiopharmaceuticals, version 2

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of brain perfusion single photon emission computed tomography (SPECT) studies using ^99mTc-labelled radiopharmaceuticals. The aim is to achieve a high quality standard for brain perfusion SPECT imaging, which will increase the diagnostic impact of this technique in clinical practice. The present document replaces a former version of the guideline published in 2001 which was inspired by the Society of Nuclear Medicine Procedure Guideline for Brain Perfusion SPECT [1], the views of the Society of Nuclear Medicine Brain Imaging Council [2], and the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.     

Antinociceptive effect of Mirabilis jalapa on acute and chronic pain models in mice

Ethnopharmacological relevance

The infusion or decoction of Mirabilis jalapa leaves is used in traditional medicine in Brazil to treat inflammatory and painful diseases. Thus, the present study was designed to investigate whether the leaf ethyl acetate (Eta) fraction from Mirabilis jalapa exhibits antinociceptive effect in clinically relevant pain models in mice. Furthermore, we have investigated the role of cholinergic system in the antinociceptive action produced by Eta in mice.

Materials and methods

The effect of Eta administered orally (10 mg/kg, p.o.) in mice was verified on the painful hypersensitivity (mechanical allodynia) in models of chronic inflammation (subcutaneous injection of complete Freund’s Adjuvant—CFA in the plantar surface of the right hind paw), postoperative (paw surgical incision) and neuropathic (partial sciatic nerve ligation) pain. In the chronic inflammation model, we further verified the effect of Eta treatment on paw edema and interleukin-1β (IL-1β) levels. We also investigated the role of muscarinic and nicotinic receptors in the antiallodynic action produced by Eta as well as the possible action of Eta on in vitro and ex vivo acetylcholinesterase activity in CFA treated animals. Furthermore, we verified the effect of Eta treatment on the parameters of liver and kidney lesion (level of urea, and activity of aspartate aminotransferase and alanine aminotransferase).

Results

Eta produced marked reduction in the allodynia caused by CFA, surgical incision and partial sciatic nerve ligation. However, Eta did not alter the paw edema or the increase of IL-1β levels produced by CFA. The antinociceptive effect of Eta was reversed by the pre-treatment of animals with the antagonists of muscarinic (atropine, 5 mg/kg, s.c) or nicotinic (mecamylamine, 0.001 mg/kg, s.c.) receptors. Eta did not alter in vitro acetylcholinesterase activity in blood or spinal cord samples, but it reversed the increase in the acetylcholinesterase activity observed in the spinal cord samples from mice injected with CFA. Moreover, Eta did not alter the indicators of liver or kidney lesion.

Conclusions

Based on its use in traditional medicine, the results of the present study confirmed the antinociceptive properties of Eta in clinically relevant pain models. Also its effect on the CFA-induced chronic inflammation seems to be related to acetylcholinesterase inhibition and cholinergic system.     

Dopaminergic mechanisms of target detection - P300 event related potential and striatal dopamine

The P300 is a cortically generated event related potential (ERP) widely used in neurophysiological research since it is related to cognitive functions and central information processing. Intracerebral recordings and functional neuroimaging studies have demonstrated that this potential is generated by various brain regions including frontal, temporal and parietal cortices. Regarding the neurochemical background, clinical and genetic investigations suggest that dopaminergic neurons could be involved in the generation of the P300. However, there is no direct evidence in vivo that P300 amplitudes and latencies are related to dopaminergic parameters. The aim of this study was to further elucidate dopaminergic aspects of the P300 ERP by combining neurophysiological and nuclear medicine assessments in vivo. Patients with a major depressive episode underwent both P300 recordings and dynamic [123I] IBZM SPECT for the evaluation of striatal dopamine D?/D?-receptor availability. There were statistically significant positive correlations of the striatal dopamine D?/D?-receptor status with P300 amplitudes and significant negative correlations with P300 latencies. Using this combined approach, the study presents direct evidence in vivo that the central dopaminergic system might play an important role in the generation of the P300 and that central dopaminergic activity could be involved in the modulation of P300 parameters. This association might be of relevance for the interpretation of P300 studies in psychiatric disorders.     

Influence of movement on FP-CIT SPECT quantification: a Monte Carlo based simulation

AIM: Head motion during acquisition is a frequently observed phenomenon while imaging the brain with SPECT. The aim of this study was to obtain detailed insight into the effects of head motion on the specific striatal binding of I-FP-CIT based on Monte Carlo simulations. MATERIALS AND METHODS: Based on the Monte Carlo code and the digital Zubal phantom, different movement profiles (angular movement in the transaxial and sagittal plane ranging from -10 to +10 degrees) were systematically simulated for normal striatal binding and neurodegeneration. A triple-headed SPECT camera equipped with low-energy, high-resolution, parallel-hole collimators was modelled for this purpose. The projection data were reconstructed iteratively and the images were then evaluated using fully automated quantification software based on morphology guided volumes of interest. In addition, data were evaluated with a method taking into account partial volume effects. RESULTS: Simulated movement resulted in blurring and streaking of the striatal structures with a concomitant change in measured specific striatal binding in most simulated profiles ranging from -44% to +2% (for the morphology guided volume of interest analyses) and -23% to +28% (for the method intended to overcome partial volume effects). In contrast to angular movement in the sagittal plane, rotation in the transaxial plane caused left/right asymmetry up to 41%. In the simulation of neurodegeneration, almost all movement profiles lead to an increase of putamen-to-caudate ratios. CONCLUSIONS: Motion during the acquisition of a SPECT scan can have an important impact on measured dopamine transporter binding with its extent varying in dependency on the method of analysis used. While this is of prime importance in a research setting, it can also have implications in clinical routine imaging.     

Mid-term results in otherwise treatment refractory primary or secondary liver confined tumours treated with selective internal radiation therapy (SIRT) using <Superscript>90</Superscript>Yttrium resin-microspheres

The purpose was to determine the response and survival and to analyse the feasibility of single-session, whole-liver SIRT in patients with non-resectable, otherwise non-responding liver cancer. Thirty-nine patients qualified for SIRT. Eighteen patients suffered from colorectal-cancer metastases (CRC), breast-cancer metastases (MBC, 7), HCC (5) and other tumours (9). Response was assessed by tumour-markers and CT-imaging. At 2-4, 5-7 and 8-9 months follow-up in 3/17, 5/15 and 5/10 of CRC-patients CEA-levels were higher than before. In the MBC group 1-3 and 4-6 months after SIRT tumour-marker-levels were higher in 2/6 and 3/3 patients, respectively. In all HCC-patients AFP-levels dropped 1-3 months after SIRT. Using RECIST, in the CRC-group progressive liver disease (PD) was found in 4/17, 2/12, 2/10 and 2/5 patients at 2-4, 5-8, 9-10 and 12-14 months follow-up. Concerning MBC, after 3 months 7/7 patients presented with stable-disease (SD) or partial-response (PR). At 5-6 months, 1/5 patients showed PD. All HCC-patients showed SD/PR at 2-3 months with no PD at 5-8 months. In the mixed-group 5/6 patients presented with SD/PR at 3-4 months and with SD in 2/3 patients at 5-6 months. The median time-to-PD was 6.5, 8.5 and 8 months for the CRC-, MBC- and mixed-group, respectively. SIRT is a promising, liver-targeted approach for patients with otherwise treatment-refractory liver tumours.     

Dopaminergic neurotransmission in patients with schizophrenia in relation to positive and negative symptoms

Schizophrenia is a complex dynamic disorder comprising a wide range of neurobiological alterations including dopaminergic dysfunction. The aim of the study was to investigate dynamic changes of dopaminergic neurotransmission in patients with schizophrenia (n=8, mean age 25.4 ± 5.8 years) in early stages of the disorder, compared to healthy control subjects (n=7, mean age 23.6 ± 2.7 years). A dynamic IBZM SPECT protocol was used to assess the endogenous dopamine release following an amphetamine challenge. Subjects received a bolus activity of 175 MBq followed by a continuous infusion of 45 MBq/h [123I]IBZM. SPECT scans were performed 2 h after bolus injection, and 1 h following the amphetamine challenge (0.3 mg/kg). Striatal IBZM binding to dopamine D2 receptors was assessed with a volume-of-interest (VOI) technique. The change in IBZM binding between pre- and post-challenge scans was used as a measure of endogenous dopamine release triggered by amphetamine. At baseline, patients showed higher mean striatal IBZM binding compared to controls (0.77 ± 0.09 vs. 0.68 ± 0.07, p=0.07). There was a statistically significant difference in IBZM binding between patients, with a predominance of negative vs. positive symptoms (0.84 ± 0.08 vs. 0.71 ± 0.04, p<0.05). Upon amphetamine challenge, mean IBZM binding decreased by about 4.9 ± 7.6% in controls (n=7) compared to a mean of 12.4 ± 5.8% in subjects with schizophrenia (p<0.05). In patients, paranoid symptoms showed a significant negative correlation with IBZM baseline binding, whereas there was a trend towards positive correlation with the decrease of IBZM binding under challenge. Negative symptoms showed positive associations with baseline IBZM binding. The data are in line with previous reports and contribute to the notion of a dynamic instability of the dopaminergic system in patients with schizophrenia, taking into account the psychopathology with respect to positive or negative symptoms.     

Loss of dopamine transporter binding in Parkinson's disease follows a single exponential rather than linear decline.

Imaging of L-dopa uptake or dopamine transporter binding can monitor the progression of Parkinson's disease. Most follow-up studies have provided data best fitted by a linear decline of their outcome measure. However, in these studies, patients were repeatedly scanned during their first years after a diagnosis had been established. METHODS: We followed 6 patients with early Parkinson's disease for 7.5 y using 123I-labeled N-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane and SPECT. RESULTS: Loss of dopamine transporter binding was best fitted using a single exponential approximation. A 63% loss (tau [time constant tau]) was calculated as 5.18 +/- 7.62 y in the putamen and 10.62 +/- 31.4 y in the caudate nucleus when a 3-parameter fit was used. CONCLUSION: These data approximate, for what is to our knowledge the first time, the decline of dopamine transporter binding as expected in biologic systems and may allow for models that correct for exponential decline to be developed and for disease-modifying effects in patients with advanced disease to be determined.     

Presynaptic dopaminergic function in patients with restless legs syndrome: Are there common features with early Parkinson's disease?

The cause of restless legs syndrome (RLS) is unknown, but an involvement of the dopaminergic system and a possible relation to Parkinson's disease (PD) is suggested by the positive response to dopaminergic treatment. We imaged the striatal dopamine transporter with [(123)I] N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(chloro-phenyl) tropane ([(123)I]IPT) and single-photon emission computed tomography (SPECT) in 28 RLS patients, and compared the results with transporter binding in 29 patients with early PD and 23 age-matched controls. No difference in IPT binding was found between RLS patients and controls. IPT binding was correlated significantly with age in RLS patients and controls, whereas there was no relation with the duration of symptoms or severity of RLS. PD patients presented significant lower presynaptic IPT binding ipsi- and contralateral to the affected body side compared with RLS patients or controls. We found no common characteristics between RLS patients and patients with early PD detectable by dopamine transporter SPECT. Our results do not strengthen an identical pathophysiologic pathway between RLS and PD on the level of nigrostriatal presynaptic terminal function.     

Neuropsychiatric symptoms in Alzheimer disease and cognitively impaired, nondemented elderly from a community-based sample in Brazil: prevalence and relationship with dementia severity.

OBJECTIVES: The objectives of this study were to describe the prevalence of neuropsychiatric symptoms of dementia in Alzheimer disease (AD) and cognitively impaired nondemented (CIND) subjects from a community-based Brazilian sample and to correlate these symptoms with severity of cognitive deficits. METHOD: A total of 1,563 randomly selected subjects were evaluated with the following screening tests: Mini-Mental Status Examination, Fuld Object Memory Evaluation, Informant Questionnaire on Cognitive Decline in the Elderly, and Activities of Daily Living-International Scale. Screen positives were submitted to a workup for dementia, physical and neurologic examination, cranial computed tomography or cerebral magnetic resonance imaging, the Cambridge Examination for Mental Disorders, Clinical Dementia Rating Scale (CDR), and the Neuropsychiatric Inventory (NPI). Diagnosis was made according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. RESULTS: Sixty patients with AD, 25 CIND, and 78 healthy elderly subjects were evaluated. Informants reported that 78.33% of patients with AD had one or more neuropsychiatric symptoms. Apathy (53.33%), depression (38.33%), sleep alterations (38.33%), and anxiety (25%) were the most prevalent disturbances in AD subjects. These disturbances were more prevalent in patients with AD than in the comparison group and CIND individuals. In the CIND group, the most frequent neuropsychiatric symptoms were anxiety and sleep alterations (both with 24%) followed by depression (16%). Total NPI scores were significantly different between AD and CIND groups, AD and comparison groups, and CIND and the comparison group. Apathy was the only neuropsychiatric symptom that was significantly different between the groups divided according to the CDR being more frequent in subjects with moderate to severe dementia. CONCLUSIONS: Neuropsychiatric symptoms seem to be as common in patients living in a developing country as they are in demented patients from the developed world. Indeed, the fact that some of our results are similar to other population-based studies may suggest that cultural factors play a minor role in the emergence of these symptoms, at least in a Latin American country like Brazil.